Despite robust evidence detailing the association of obesity on the gut microbiome, little is known about the role obesity plays in modulating the oral microbiome. The obesity epidemic continues to globally grow, nearly doubling in the last 30 years to include over half a billion individuals (WHO). The WHO region with the highest obesity rate is the Americas where more than one-third of U.S. adults are clinically obese (CDC). The incidence of periodontitis is greater among overweight and obese individuals as compared to normal weight individuals. Therefore, it is important to understand how these environmental factors shape the oral microbiome in health, and thereby protects or predisposes the individual to disease. The oral cavity is a milieu where environmental factors, the microbiome, and host interact in a complex ways to impact health and disease. Continuous perturbations of this oral ecosystem by various environmental factors often result in changes to both the host and the residing bacterial communities. Thus, we hypothesize that the composition and functional potential of the oral metagenome is distinct in an obese population, and can be modified following weight loss. We propose to test the hypothesis with a multi-arm, cross-sectional study combined with a longitudinal evaluation. First, we will use a quantitative, open-ended approach (next-generation shotgun sequencing) to characterize the community and its genetic content in obese and normal-weight individuals. An initial step in demonstrating a causal relationship between obesity and changes in the oral microbiome would be to explore if a temporal relationship exists between the two. Therefore, we will follow a subset of the population following bariatric surgery to establish a temporal relationship between obesity and the oral metagenome using shotgun sequencing and computational bioinformatics, combined with clinical and molecular biomarkers of obesity. This characterization will also provide baseline information for further studies examining host-bacterial interactions in this microenvironment as well as functional and mechanistic investigations on the candidates identified here.